Diuretics – Pharmacology – Merck Veterinary Manual

By Sonya G. Gordon, DVM, DVSc, DACVIM (Cardiology), Associate Professor, Department of Small Animal Clinical Science, Texas A and M University Ashley B. Saunders, DVM, DACVIM (Cardiology), Associate Professor of Cardiology, College of Veterinary Medicine and Biomedical Sciences, Texas A and M University

Diuretics are the cornerstone of therapy in management of animals with congestive heart failure (CHF) characterized by cardiogenic pulmonary edema, pleural effusion, ascites, or a combination of these signs. Three classes of diuretics are used to treat CHF in dogs and cats: loop diuretics, thiazide diuretics, and potassium-sparing diuretics. They differ in their relative potency and mechanisms of action. The loop diuretics are the most potent and have a high ceiling, enabling them to be used in a dose-dependent way to treat mild to life-threatening CHF. Additionally, they can be administered orally or parenterally. Thiazide diuretics are mild to moderate in potency. They are typically used in conjunction with a loop diuretic (eg, furosemide) in animals with severe refractory CHF. Historically, the use of potassium-sparing diuretics (eg, spironolactone) has been reserved for those animals that have right heart failure or have become hypokalemic secondary to the use of other diuretics, or for those animals refractory to other agents.

All diuretics share a similar adverse effect profile, including electrolyte and acid-base disturbances, dehydration, and prerenal and renal azotemia. The relative risk of azotemia is increased when a diuretic is used concurrently with an angiotensin-converting enzyme (ACE) inhibitor and/or an NSAID or other potential renal toxin. Diuretics may also increase the risk of digoxin toxicity. In addition, diuretic resistance can develop with longterm treatment. The most common electrolyte and acid-base abnormalities include hypokalemia, hyponatremia, hypomagnesemia, and metabolic alkalosis. These effects are potentiated by the use of more than one diuretic (sequential nephron blockade), concurrent hyporexia/anorexia, and the use of higher doses. Typically, potential adverse effects are more severe in cats than in dogs.

Numerous factors determine the response to diuretic therapy. These include the potency of the drug, the dosage administered, the duration of action of the drug, the route of administration, renal blood flow, glomerular filtration rate, and nephron function. The plasma concentration depends on the route of administration (IV administration will produce a higher concentration than PO administration) and the dose. The duration of effect will also determine the total diuretic effect produced in a certain time period.

Animals with CHF may become refractory to furosemide because of decreased delivery of the drug to the nephron as a result of reduced renal blood flow or hormonal stimulus for sodium and water retention. Therefore, strategies to increase renal blood flow and/or plasma concentration may ameliorate diuretic resistance.

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Diuretics - Pharmacology - Merck Veterinary Manual